Transplant Flashcards
Define autologous
“self”
Define allogeneic
“person to person”
Define xenogeneic
“across species”
Define hyperacute rejection
Robust reaction that occurs within minutes (major barrier to xenotransplantation, not common in clinical transplant)
Define acute rejection
Occurs within days to weeks in non-immune suppressed individuals or months to years in suppressed pts
**can be cellular or humoral in nature (T cell or Ab mediated)
Define chronic rejection
Occurs months to years after transplant (now the major cause of graft failure)
Characterized by:
- vascular changes
- intersitital fibrosis
- loss of renal parenchyma -> renal ischemia
- interstitial fibrosis
- tubular atrophy
Define chimerism
Mixture of donor and self
What are transplantation antigens?
Human leukocyte antigen (HLA; another name for the human MHC molecules)
*For hematopoietic stem cell grafts, “minor” histocompatibility antigens can be targets
What are the MHC alleles?
6 class I MHC alleles
6 class II MHC alleles (HLA-DR, HLA-DQ, HLA-DP; 3 from each parent)
(HLA-A, HLA-B, and HLA-C; 3 from each parent)
How are MHC proteins matched for transplant?
All MHC proteins can be targets for rejection, but HLA-C and HLA-DP are less important
*Many types of organ transplants no longer MHC match because of the ability to suppress the immune system with drugs
**Matching is still important for hematopoietic stem cell transplants
What is the difference between direct and indirect alloantigen recognition?
Direct= Alloreactive T cell recognizes allogenic MHC (regardless of antigen being presented) on allogenic APC that was transferred in the transplant
Indirect= Recipient APC recognizes foreign MHC on allogenic APC, phagocytoses it, degrades and presents on self MHC to alloreactive T cell (foreign processed peptide recognized)
What is the MOA of cyclosporine graft rejection prevention?
Blocks T cell cytokine production by inhibiting the phosphatase calcineurin and thus blocking activation of the NFAT transcription factor
What are the sources of HSCs?
Hematopoietic stem cells
Historically obtained from bone marrow
Also from peripheral blood (after mobilization by growth factors/chemokine receptor inhibitors) or cord blood
With HSCT, can graft rejection or graft versus host occur?
In hematopoietic stem cell transplant, BOTH host-anti-donor (graft rejection) and donor-anti-host rejection (graft vs host disease) can occur
What are minor histocompatibility antigens (miHA)?
Less potent “minor” antigens that can induce rejection; cleaved and processed endogenous proteins that occupy the binding groove of MHC class I and II molecules
*Genetic polymorphism= principal determinant whether a self peptide can be a miHA; majority due to SNPs
**cumulative; multiple miHAs=major
What are some of the immune problems associated with transplant of allogenic HSCs?
- finding a suitable donor (histocompatiblity)
- graft vs host disease
- risk for infection (immune deficiency before WBCs return to normal)
- graft rejection
- malignant disease relapse
- slow immune recovery (esp for older patients)
How is graft vs host disease classified?
Given a grade (I being least severe, IV being most severe) based on the extent of involvement of key target tissues such as skin, liver, and GI
What drives GVHD?
Driven by donor T cells
**a bigger problem than recipient-anti-donor rejection
What type of rejection is predominant in solid organ transplant? What type of antigen drives this rejection?
Recipient-anti-donor
Acute driven by recipient T cells (can involve B cells/Abs)
Chronic rejection can involve CD4 T cells and B cells
**MHC (major) drives rejection, minor HAs not as important
What type of antigen drives rejection in HSCT?
Both major (MHC) and minor HAs (miHA) play important roles in alloreactivity with stem cells
*recall in solid organ MHC drives rejection
